Sex differences in the predictors of skeletal muscle microvascular reactivity in older individuals

Aging is associated with an increased risk of cardiovascular disease and vascular dysfunction. Reduced nitric oxide bioavailability is considered one of the key mechanisms underlying vascular dysfunction in large arteries of older adults. However, the relationship between cardiovascular disease risk factors, nitric oxide bioavailability, and skeletal muscle microvascular reactivity, an early hallmark in cardiovascular disease progression, is unclear in older individuals. Also uncertain is whether this relationship is influenced by sex. Therefore, this study assessed the association between cardiovascular disease risk factors, circulating markers of nitric oxide availability (plasma nitrate and nitrite), and skeletal muscle microvascular reactivity in older individuals. First, we confirmed in a cohort of young and older individuals that aging is associated with skeletal muscle microvascular dysfunction. Next, we observed that skeletal muscle microvascular reactivity (P = 0.653; η² = 0.016) and circulating nitric oxide metabolites (Nitrate: P = 0.641, η² = 0.011; Nitrite: P = 0.560, η² = 0.017; NOx: P = 0.639, η² = 0.011) did not differ between older males and females. Finally, using multivariate regression models, we found that: (i) the number of cardiovascular risk factors was negatively associated with skeletal muscle microvascular reactivity in older males and females (B = -0.132, P = 0.044); (ii) the relationship between plasma nitrite and skeletal muscle microvascular reactivity was influenced by sex (F = 6.837, P = 0.016); and (iii) skeletal muscle microvascular reactivity in older females displayed a strong positive association with plasma nitrite (R² = 0.720, P < 0.001). While the impact of cardiovascular disease risk factors on skeletal muscle microvascular reactivity was not influenced by sex, sex-related discrepancies were found in the relationship between nitric oxide bioavailability and skeletal muscle microvascular reactivity in older individuals.